Primary Cutaneous Follicle Center Lymphoma

  • Amrita Goyal
  • Joi B. Carter
  • Jeffrey A. Barnes
  • Lyn McDivitt DuncanEmail author


Primary cutaneous follicle center lymphoma (pcFCL) is an indolent B-cell lymphoma with a remarkably good prognosis. This neoplasm of mature germinal center B cells constitutes 60 % of all primary cutaneous B-cell lymphomas and 9–11 % of all cutaneous lymphomas [1, 2]. It also includes 5 % of all follicular lymphomas, nodal and extranodal [3]. It typically presents with firm, erythematous to violaceous papules, plaques, and tumors on the scalp, trunk, and upper extremities. When it occurs on the back, it has been referred to in the past as Crosti lymphoma or reticulohistiocytoma of the dorsum [1, 4]. Differentiation of pcFCL from systemic follicle center lymphomas is critical, given the substantially worse prognosis of systemic follicle center lymphomas. This chapter addresses the clinical presentation, prognosis, treatment, histopathology, immunophenotype, and differential diagnosis of pcFCL. It closes with two clinical cases, including clinical images and histopathology.


Primary cutaneous follicle center lymphoma Follicular lymphoma Crosti’s CD20 Bcl2 Bcl6 Naked follicles Inside-out follicles MALT lymphoma Diffuse large B-cell lymphoma Cutaneous lymphoma hyperplasia Pseudolymphoma 


  1. 1.
    Willemze R, Swerdlow SH, Harris NL, Vergier B. Primary cutaneous follicle centre lymphoma. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO classification of tumors haematopathol lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer; 2008. p. 227–8.Google Scholar
  2. 2.
    Swerdlow SH, Quintanilla-Martinez L, Willemze R, Kinney MC. Cutaneous B-cell lymphoproliferative disorders: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop. Am J Clin Pathol. 2013;139:515–35.PubMedCrossRefGoogle Scholar
  3. 3.
    Fernán de zdeLarrea C, Martínez-Pozo A, Mercadal S, García A, Gutierrez-García G, Valera A, et al. Initial features and outcome of cutaneous and non-cutaneous primary extranodal follicular lymphoma. Br J Haematol. 2011;153:334–40.CrossRefGoogle Scholar
  4. 4.
    Gulia A, Saggini A, Wiesner T, Fink-Puches R, Argenyi Z, Ferrara G, et al. Clinicopathologic features of early lesions of primary cutaneous follicle center lymphoma, diffuse type: implications for early diagnosis and treatment. J Am Acad Dermatol. 2011;65:991–1000.PubMedCrossRefGoogle Scholar
  5. 5.
    Hamilton SN, Wai ES, Tan K, Alexander C, Gascoyne RD, Connors JM. Treatment and outcomes in patients with primary cutaneous B-cell lymphoma: the BC Cancer Agency experience. Int J Radiat Oncol. 2013;87:719–25.CrossRefGoogle Scholar
  6. 6.
    Senff NJ, Hoefnagel JJ, Jansen PM, Vermeer MH, van Baarlen J, Blokx WA, et al. Reclassification of 300 primary cutaneous B-Cell lymphomas according to the new WHO-EORTC classification for cutaneous lymphomas: comparison with previous classifications and identification of prognostic markers. J Clin Oncol. 2007;25:1581–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Massone C, Chott A, Metze D, Kerl K, Citarella L, Vale E. Subcutaneous, blastic natural killer (NK), NK/T-cell, and other cytotoxic lymphomas of the skin: a morphologic, immunophenotypic, and molecular study of 50 patients. Am J Surg Pathol. 2004;28:719–35.PubMedCrossRefGoogle Scholar
  8. 8.
    Senff NJ, Hoefnagel JJ, Neelis KJ, Vermeer MH, Noordijk EM, Willemze R. Results of radiotherapy in 153 primary cutaneous B-Cell lymphomas classified according to the WHO-EORTC classification. Arch Dermatol. 2007;143:1520–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Senff NJ, Noordijk EM, Kim YH, Bagot M, Berti E, Cerroni L, et al. European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas. Blood. 2008;112:1600–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Fernandez-Flores A, Smucler-Simonovich A, Escalante F, Manjon JA. The differential diagnosis between primary cutaneous large B-cell lymphoma and cutaneous follicular lymphoma: prognostic and therapeutic implications. Am J Dermatopathol. 2011;33:819–26.PubMedCrossRefGoogle Scholar
  11. 11.
    Bekkenk MW, Vermeer MH, Geerts ML, Noordijk EM, Heule F, van Voorst Vader PC, et al. Treatment of multifocal primary cutaneous B-cell lymphoma: a clinical follow-up study of 29 patients. J Clin Oncol. 1999;17:2471–8.PubMedGoogle Scholar
  12. 12.
    Quéreux G, Brocard A, Peuvrel L, Nguyen JM, Knol A-C, Dréno B. Systemic rituximab in multifocal primary cutaneous follicle centre lymphoma. Acta Derm Venereol. 2011;91:562–7.PubMedGoogle Scholar
  13. 13.
    Ceovic R, Jovanovic I, Kostovic K, Rados J, Dotlic S, Radman I, et al. Radiotherapy of primary cutaneous follicle center lymphoma: case report and review of literature. Radiat Oncol. 2013;8:147.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    De Leval L, Harris NL, Longtine J, Ferry JA, Duncan LM. Cutaneous B-cell lymphomas of follicular and marginal zone types: use of Bcl-6, CD10, Bcl-2, and CD21 in diagnosis and classification. Am J Surg Pathol. 2001;25:732–41.PubMedCrossRefGoogle Scholar
  15. 15.
    Gellrich S, Rutz S, Golembowski S, Jacobs C, von Zimmermann M, Lorenz P, et al. Primary cutaneous follicle center cell lymphomas and large B cell lymphomas of the leg descend from germinal center cells. A single cell polymerase chain reaction analysis. J Invest Dermatol. 2001;117:1512–20.PubMedCrossRefGoogle Scholar
  16. 16.
    Hoefnagel JJ, Dijkman R, Basso K, Jansen PM, Hallermann C, Willemze R, et al. Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling. Blood. 2005;105:3671–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Hoefnagel JJ, Vermeer MH, Jansen PM, Fleuren GJ, Meijer CJLM, Willemze R. Bcl-2, Bcl-6 and CD10 expression in cutaneous B-cell lymphoma: further support for a follicle centre cell origin and differential diagnostic significance. Br J Dermatol. 2003;149:1183–91.PubMedCrossRefGoogle Scholar
  18. 18.
    Fujiwara M, Morales AV, Seo K, Kim YH, Arber DA. Sundram UN Clonal identity and differences in primary cutaneous B-cell lymphoma occurring at different sites or time points in the same patient. Am J Dermatopathol. 2013;35:11–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Dijkman R, Tensen CP, Jordanova ES, Knijnenburg J, Hoefnagel JJ, Mulder AA, et al. Array-based comparative genomic hybridization analysis reveals recurrent chromosomal alterations and prognostic parameters in primary cutaneous large B-cell lymphoma. J Clin Oncol. 2006;24:296–305.PubMedCrossRefGoogle Scholar
  20. 20.
    Child FJ, Russell-Jones R, Woolford AJ, Calonje E, Photiou A, Orchard G, et al. Absence of the t(14;18) chromosomal translocation in primary cutaneous B-cell lymphoma. Br J Dermatol. 2001;144:735–44.PubMedCrossRefGoogle Scholar
  21. 21.
    Hallermann C, Kaune KM, Gesk S, Martin-Subero JI, Gunawan B, Griesinger F, et al. Molecular cytogenetic analysis of chromosomal breakpoints in the IGH, MYC, BCL6, and MALT1 gene loci in primary cutaneous B-cell lymphomas. J Invest Dermatol. 2004;123:213–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Mirza I, Macpherson N. Primary cutaneous follicular lymphoma: an assessment of clinical, histopathologic, immunophenotypic, and molecular features. J Clin Oncol. 2002;20:647–55.PubMedCrossRefGoogle Scholar
  23. 23.
    Cerroni L, Arzberger E, Pütz B, Höfler G, Metze D, Sander CA, et al. Primary cutaneous follicle center cell lymphoma with follicular growth pattern. Blood. 2000;95:3922–8.PubMedGoogle Scholar
  24. 24.
    Isaacson P, Chott A, Nakamura S, Muller-Hermelink HK, Harris NL, Swerdlow SH. Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO classification of tumors haematopathol lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer; 2008. p. 214–7.Google Scholar
  25. 25.
    Cerroni L, Signoretti S, Höfler G, Annessi G, Pütz B, Lackinger E, et al. Primary cutaneous marginal zone B-cell lymphoma: a recently described entity of low-grade malignant cutaneous B-cell lymphoma. Am J Surg Pathol. 1997;21:1307–15.PubMedCrossRefGoogle Scholar
  26. 26.
    Demirkesen C, Tüzüner N, Esen T, Lebe B, Ozkal S. The expression of IgM is helpful in the differentiation of primary cutaneous diffuse large B cell lymphoma and follicle center lymphoma. Leuk Res. 2011;35:1269–72.PubMedCrossRefGoogle Scholar
  27. 27.
    Jaffe ES, Harris NL, Stein H, Campo E, Pileri SA, Swerdlow SH. Introduction and overview of the classification of the lymphoid neoplasms. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO classification of tumors haematopathol lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer; 2008. p. 158–66.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Amrita Goyal
    • 1
  • Joi B. Carter
    • 2
  • Jeffrey A. Barnes
    • 3
  • Lyn McDivitt Duncan
    • 4
    Email author
  1. 1.Harvard-MIT Division of Health Sciences and TechnologyHarvard Medical SchoolBostonUSA
  2. 2.Department of DermatologyMassachusetts General Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Comprehensive Cutaneous Lymphoma Program, Department of MedicineMassachusetts General Hospital Cancer CenterBostonUSA
  4. 4.Dermatopathology Service, Department of PathologyMassachusetts General Hospital, Harvard Medical SchoolBostonUSA

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